Thrombosis

Adapted D-dimer thresholds based on pretest probability were effective for ruling out pulmonary embolism (PE) in subgroups of high-risk individuals without the use of imaging in a review of data.

In a patient suspected to have a PE, “diagnosis is made radiographically, usually with CT pulmonary angiogram, or V/Q scan,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview.

“Validated clinical decision tools such as Wells’ score or Geneva score may be used to identify patients at low pretest probability of PE who may initially get a D-dimer level check, followed by imaging only if D-dimer level is elevated,” explained Dr. Pal, who was not involved with the new research, which was published in the Annals of Internal Medicine.

According to the authors of the new paper, while current diagnostic strategies in patients with suspected PE include use of a validated clinical decision rule (CDR) and D-dimer testing to rule out PE without imaging tests, the effectiveness of D-dimer tests in older patients, inpatients, cancer patients, and other high-risk groups has not been well-studied.

Lead author of the paper, Milou A.M. Stals, MD, and colleagues said their goal was to evaluate the safety and efficiency of the Wells rule and revised Geneva score in combination with D-dimer tests, and also the YEARS algorithm for D-dimer thresholds, in their paper.

Dr. Stals, of Leiden (the Netherlands) University Medical Center, and the coinvestigators conducted an international systemic review and individual patient data meta-analysis that included 16 studies and 20,553 patients, with all studies having been published between Jan. 1, 1995, and Jan. 1, 2021. Their primary outcomes were the safety and efficiency of each of these three strategies.

In the review, the researchers defined safety as the 3-month incidence of venous thromboembolism after PE was ruled out without imaging at baseline. They defined efficiency as the proportion patients for whom PE was ruled out based on D-dimer thresholds without imaging.

Overall, efficiency was highest in the subset of patients aged younger than 40 years, ranging from 47% to 68% in this group. Efficiency was lowest in patients aged 80 years and older (6.0%-23%), and in patients with cancer (9.6%-26%).

The efficiency was higher when D-dimer thresholds based on pretest probability were used, compared with when fixed or age-adjusted D-dimer thresholds were used.

The key finding was the significant variability in performance of the diagnostic strategies, the researchers said.

“The predicted failure rate was generally highest for strategies incorporating adapted D-dimer thresholds. However, at the same time, predicted overall efficiency was substantially higher with these strategies versus strategies with a fixed D-dimer threshold as well,” they said. Given that the benefits of each of the three diagnostic strategies depends on their correct application, the researchers recommended that an individual hospitalist choose one strategy for their institution.

“Whether clinicians should rely on the Wells rule, the YEARS algorithm, or the revised Geneva score becomes a matter of local preference and experience,” Dr. Stals and colleagues wrote.

The study findings were limited by several factors including between-study differences in scoring predictors and D-dimer assays. Another limitation was that differential verification biases for classifying fatal events and PE may have contributed to overestimation of failure rates of the adapted D-dimer thresholds.

Strengths of the study included its large sample size and original data on pretest probability, and that data support the use of any of the three strategies for ruling out PE in the identified subgroups without the need for imaging tests, the authors wrote.

“Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies,” they concluded.

Adapted D-dimer benefits some patients

“Clearly, increasing the D-dimer cutoff will lower the number of patients who require radiographic imaging (improved specificity), but this comes with a risk for missing PE (lower sensitivity). Is this risk worth taking?” Daniel J. Brotman, MD, of Johns Hopkins University, Baltimore, asked in an editorial accompanying the new study.

Dr. Brotman was not surprised by the study findings.

“Conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis,” he said. However, these patients are unlikely to have normal D-dimer levels regardless of the cutoff used.

Adapted D-dimer cutoffs may benefit some patients, including those with contraindications or limited access to imaging, said Dr. Brotman. D-dimer may be used for risk stratification regardless of PE, since patients with marginally elevated D-dimers have better prognoses than those with higher D-dimer elevations, even if a small PE is missed.

Dr. Brotman wrote that increasing D-dimer cutoffs for high-risk patients in the subgroups analyzed may spare some patients radiographic testing, but doing so carries an increased risk for diagnostic failure. Overall, “the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”
 

Focus on single strategy ‘based on local needs’

“Several validated clinical decision tools, along with age or pretest probability adjusted D-dimer threshold are currently in use as diagnostic strategies for ruling out pulmonary embolism,” Dr. Pal said in an interview.

The current study is important because of limited data on the performance of these strategies in specific subgroups of patients whose risk of PE may differ from the overall patient population, he noted.

“Different diagnostic strategies for PE have a variable performance in patients with differences of age, active cancer, and history of VTE,” said Dr. Pal. “However, in this study, no clear preference for one strategy over others could be established for these subgroups, and clinicians should continue to follow institution-specific guidance.

“A single strategy should be adopted at each institution based on local needs and used as the standard of care until further data are available,” he said.

“The use of D-dimer to rule out PE, either with fixed threshold or age-adjusted thresholds, can be confounded in clinical settings by other comorbid conditions such as sepsis, recent surgery, and more recently, COVID-19,” he said.

“Since the findings of this study do not show a clear benefit of one diagnostic strategy over others in the analyzed subgroups of patients, further prospective head-to-head comparison among the subgroups of interest would be helpful to guide clinical decision making,” Dr. Pal added.
 

YEARS-specific study supports D-dimer safety and value

A recent paper published in JAMA supported the results of the meta-analysis. In that study, Yonathan Freund, MD, of Sorbonne Université, Paris, and colleagues focused on the YEARS strategy combined with age-adjusted D-dimer thresholds as a way to rule out PE in PERC-positive ED patients.

The authors of this paper randomized 18 EDs to either a protocol of intervention followed by control, or control followed by intervention. The study population included 726 patients in the intervention group and 688 in the control group.

The intervention strategy to rule out PE consisted of assessing the YEARS criteria and D-dimer testing. PE was ruled out in patients with no YEARS criteria and a D-dimer level below 1,000 ng/mL and in patients with one or more YEARS criteria and D-dimers below an age-adjusted threshold (defined as age times 10 ng/mL in patients aged 50 years and older).

The control strategy consisted of D-dimer testing for all patients with the threshold at age-adjusted levels; D-dimers about these levels prompted chest imaging.

Overall, the risk of a missed VTE at 3 months was noninferior between the groups (0.15% in the intervention group and 0.80% in the controls).

“The intervention was associated with a statistically significant reduction in chest imaging use,” the researchers wrote.

This study’s findings were limited by randomization at the center level, rather than the patient level, and the use of imaging on some patients despite negative D-dimer tests, the researchers wrote. However, their findings support those of previous studies and especially support the safety of the intervention, in an emergency medicine setting, as no PEs occurred in patients with a YEARS score of zero who underwent the intervention.
 

Downsides to applying algorithms to every patient explained

In an editorial accompanying the JAMA study, Marcel Levi, MD, and Nick van Es, MD, of Amsterdam University Medical Center, emphasized the challenges of diagnosing PE given that many patients present with nonspecific clinical manifestations and without typical signs and symptoms. High-resolution CT pulmonary angiography allows for a fast and easy diagnosis in an emergency setting. However, efforts are ongoing to develop alternative strategies that avoid unnecessary scanning for potential PE patients, many of whom have alternative diagnoses such as pulmonary infections, cardiac conditions, pleural disease, or musculoskeletal problems.

On review of the JAMA study using the YEARS rule with adjusted D-dimer thresholds, the editorialists noted that the data were robust and indicated a 10% reduction in chest imaging. They also emphasized the potential to overwhelm busy clinicians with more algorithms.

“Blindly applying algorithms to every patient may be less appropriate or even undesirable in specific situations in which deviation from the rules on clinical grounds is indicated,” but a complex imaging approach may be time consuming and challenging in the acute setting, and a simple algorithm may be safe and efficient in many cases, they wrote. “From a patient perspective, a negative diagnostic algorithm for pulmonary embolism does not diminish the physician’s obligation to consider other diagnoses that explain the symptoms, for which chest CT scans may still be needed and helpful.”

The Annals of Internal Medicine study was supported by the Dutch Research Council. The JAMA study was supported by the French Health Ministry. Dr. Stals, Dr. Freund, Dr. Pal, Dr. Levi, and Dr. van Es had no financial conflicts to disclose.

Adapted D-dimer thresholds based on pretest probability were effective for ruling out pulmonary embolism (PE) in subgroups of high-risk individuals without the use of imaging in a review of data.

In a patient suspected to have a PE, “diagnosis is made radiographically, usually with CT pulmonary angiogram, or V/Q scan,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview.

“Validated clinical decision tools such as Wells’ score or Geneva score may be used to identify patients at low pretest probability of PE who may initially get a D-dimer level check, followed by imaging only if D-dimer level is elevated,” explained Dr. Pal, who was not involved with the new research, which was published in the Annals of Internal Medicine.

According to the authors of the new paper, while current diagnostic strategies in patients with suspected PE include use of a validated clinical decision rule (CDR) and D-dimer testing to rule out PE without imaging tests, the effectiveness of D-dimer tests in older patients, inpatients, cancer patients, and other high-risk groups has not been well-studied.

Lead author of the paper, Milou A.M. Stals, MD, and colleagues said their goal was to evaluate the safety and efficiency of the Wells rule and revised Geneva score in combination with D-dimer tests, and also the YEARS algorithm for D-dimer thresholds, in their paper.

Dr. Stals, of Leiden (the Netherlands) University Medical Center, and the coinvestigators conducted an international systemic review and individual patient data meta-analysis that included 16 studies and 20,553 patients, with all studies having been published between Jan. 1, 1995, and Jan. 1, 2021. Their primary outcomes were the safety and efficiency of each of these three strategies.

In the review, the researchers defined safety as the 3-month incidence of venous thromboembolism after PE was ruled out without imaging at baseline. They defined efficiency as the proportion patients for whom PE was ruled out based on D-dimer thresholds without imaging.

Overall, efficiency was highest in the subset of patients aged younger than 40 years, ranging from 47% to 68% in this group. Efficiency was lowest in patients aged 80 years and older (6.0%-23%), and in patients with cancer (9.6%-26%).

The efficiency was higher when D-dimer thresholds based on pretest probability were used, compared with when fixed or age-adjusted D-dimer thresholds were used.

The key finding was the significant variability in performance of the diagnostic strategies, the researchers said.

“The predicted failure rate was generally highest for strategies incorporating adapted D-dimer thresholds. However, at the same time, predicted overall efficiency was substantially higher with these strategies versus strategies with a fixed D-dimer threshold as well,” they said. Given that the benefits of each of the three diagnostic strategies depends on their correct application, the researchers recommended that an individual hospitalist choose one strategy for their institution.

“Whether clinicians should rely on the Wells rule, the YEARS algorithm, or the revised Geneva score becomes a matter of local preference and experience,” Dr. Stals and colleagues wrote.

The study findings were limited by several factors including between-study differences in scoring predictors and D-dimer assays. Another limitation was that differential verification biases for classifying fatal events and PE may have contributed to overestimation of failure rates of the adapted D-dimer thresholds.

Strengths of the study included its large sample size and original data on pretest probability, and that data support the use of any of the three strategies for ruling out PE in the identified subgroups without the need for imaging tests, the authors wrote.

“Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies,” they concluded.

Adapted D-dimer benefits some patients

“Clearly, increasing the D-dimer cutoff will lower the number of patients who require radiographic imaging (improved specificity), but this comes with a risk for missing PE (lower sensitivity). Is this risk worth taking?” Daniel J. Brotman, MD, of Johns Hopkins University, Baltimore, asked in an editorial accompanying the new study.

Dr. Brotman was not surprised by the study findings.

“Conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis,” he said. However, these patients are unlikely to have normal D-dimer levels regardless of the cutoff used.

Adapted D-dimer cutoffs may benefit some patients, including those with contraindications or limited access to imaging, said Dr. Brotman. D-dimer may be used for risk stratification regardless of PE, since patients with marginally elevated D-dimers have better prognoses than those with higher D-dimer elevations, even if a small PE is missed.

Dr. Brotman wrote that increasing D-dimer cutoffs for high-risk patients in the subgroups analyzed may spare some patients radiographic testing, but doing so carries an increased risk for diagnostic failure. Overall, “the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”
 

Focus on single strategy ‘based on local needs’

“Several validated clinical decision tools, along with age or pretest probability adjusted D-dimer threshold are currently in use as diagnostic strategies for ruling out pulmonary embolism,” Dr. Pal said in an interview.

The current study is important because of limited data on the performance of these strategies in specific subgroups of patients whose risk of PE may differ from the overall patient population, he noted.

“Different diagnostic strategies for PE have a variable performance in patients with differences of age, active cancer, and history of VTE,” said Dr. Pal. “However, in this study, no clear preference for one strategy over others could be established for these subgroups, and clinicians should continue to follow institution-specific guidance.

“A single strategy should be adopted at each institution based on local needs and used as the standard of care until further data are available,” he said.

“The use of D-dimer to rule out PE, either with fixed threshold or age-adjusted thresholds, can be confounded in clinical settings by other comorbid conditions such as sepsis, recent surgery, and more recently, COVID-19,” he said.

“Since the findings of this study do not show a clear benefit of one diagnostic strategy over others in the analyzed subgroups of patients, further prospective head-to-head comparison among the subgroups of interest would be helpful to guide clinical decision making,” Dr. Pal added.
 

YEARS-specific study supports D-dimer safety and value

A recent paper published in JAMA supported the results of the meta-analysis. In that study, Yonathan Freund, MD, of Sorbonne Université, Paris, and colleagues focused on the YEARS strategy combined with age-adjusted D-dimer thresholds as a way to rule out PE in PERC-positive ED patients.

The authors of this paper randomized 18 EDs to either a protocol of intervention followed by control, or control followed by intervention. The study population included 726 patients in the intervention group and 688 in the control group.

The intervention strategy to rule out PE consisted of assessing the YEARS criteria and D-dimer testing. PE was ruled out in patients with no YEARS criteria and a D-dimer level below 1,000 ng/mL and in patients with one or more YEARS criteria and D-dimers below an age-adjusted threshold (defined as age times 10 ng/mL in patients aged 50 years and older).

The control strategy consisted of D-dimer testing for all patients with the threshold at age-adjusted levels; D-dimers about these levels prompted chest imaging.

Overall, the risk of a missed VTE at 3 months was noninferior between the groups (0.15% in the intervention group and 0.80% in the controls).

“The intervention was associated with a statistically significant reduction in chest imaging use,” the researchers wrote.

This study’s findings were limited by randomization at the center level, rather than the patient level, and the use of imaging on some patients despite negative D-dimer tests, the researchers wrote. However, their findings support those of previous studies and especially support the safety of the intervention, in an emergency medicine setting, as no PEs occurred in patients with a YEARS score of zero who underwent the intervention.
 

Downsides to applying algorithms to every patient explained

In an editorial accompanying the JAMA study, Marcel Levi, MD, and Nick van Es, MD, of Amsterdam University Medical Center, emphasized the challenges of diagnosing PE given that many patients present with nonspecific clinical manifestations and without typical signs and symptoms. High-resolution CT pulmonary angiography allows for a fast and easy diagnosis in an emergency setting. However, efforts are ongoing to develop alternative strategies that avoid unnecessary scanning for potential PE patients, many of whom have alternative diagnoses such as pulmonary infections, cardiac conditions, pleural disease, or musculoskeletal problems.

On review of the JAMA study using the YEARS rule with adjusted D-dimer thresholds, the editorialists noted that the data were robust and indicated a 10% reduction in chest imaging. They also emphasized the potential to overwhelm busy clinicians with more algorithms.

“Blindly applying algorithms to every patient may be less appropriate or even undesirable in specific situations in which deviation from the rules on clinical grounds is indicated,” but a complex imaging approach may be time consuming and challenging in the acute setting, and a simple algorithm may be safe and efficient in many cases, they wrote. “From a patient perspective, a negative diagnostic algorithm for pulmonary embolism does not diminish the physician’s obligation to consider other diagnoses that explain the symptoms, for which chest CT scans may still be needed and helpful.”

The Annals of Internal Medicine study was supported by the Dutch Research Council. The JAMA study was supported by the French Health Ministry. Dr. Stals, Dr. Freund, Dr. Pal, Dr. Levi, and Dr. van Es had no financial conflicts to disclose.

Adapted D-dimer thresholds based on pretest probability were effective for ruling out pulmonary embolism (PE) in subgroups of high-risk individuals without the use of imaging in a review of data.

In a patient suspected to have a PE, “diagnosis is made radiographically, usually with CT pulmonary angiogram, or V/Q scan,” Suman Pal, MD, of the University of New Mexico, Albuquerque, said in an interview.

“Validated clinical decision tools such as Wells’ score or Geneva score may be used to identify patients at low pretest probability of PE who may initially get a D-dimer level check, followed by imaging only if D-dimer level is elevated,” explained Dr. Pal, who was not involved with the new research, which was published in the Annals of Internal Medicine.

According to the authors of the new paper, while current diagnostic strategies in patients with suspected PE include use of a validated clinical decision rule (CDR) and D-dimer testing to rule out PE without imaging tests, the effectiveness of D-dimer tests in older patients, inpatients, cancer patients, and other high-risk groups has not been well-studied.

Lead author of the paper, Milou A.M. Stals, MD, and colleagues said their goal was to evaluate the safety and efficiency of the Wells rule and revised Geneva score in combination with D-dimer tests, and also the YEARS algorithm for D-dimer thresholds, in their paper.

Dr. Stals, of Leiden (the Netherlands) University Medical Center, and the coinvestigators conducted an international systemic review and individual patient data meta-analysis that included 16 studies and 20,553 patients, with all studies having been published between Jan. 1, 1995, and Jan. 1, 2021. Their primary outcomes were the safety and efficiency of each of these three strategies.

In the review, the researchers defined safety as the 3-month incidence of venous thromboembolism after PE was ruled out without imaging at baseline. They defined efficiency as the proportion patients for whom PE was ruled out based on D-dimer thresholds without imaging.

Overall, efficiency was highest in the subset of patients aged younger than 40 years, ranging from 47% to 68% in this group. Efficiency was lowest in patients aged 80 years and older (6.0%-23%), and in patients with cancer (9.6%-26%).

The efficiency was higher when D-dimer thresholds based on pretest probability were used, compared with when fixed or age-adjusted D-dimer thresholds were used.

The key finding was the significant variability in performance of the diagnostic strategies, the researchers said.

“The predicted failure rate was generally highest for strategies incorporating adapted D-dimer thresholds. However, at the same time, predicted overall efficiency was substantially higher with these strategies versus strategies with a fixed D-dimer threshold as well,” they said. Given that the benefits of each of the three diagnostic strategies depends on their correct application, the researchers recommended that an individual hospitalist choose one strategy for their institution.

“Whether clinicians should rely on the Wells rule, the YEARS algorithm, or the revised Geneva score becomes a matter of local preference and experience,” Dr. Stals and colleagues wrote.

The study findings were limited by several factors including between-study differences in scoring predictors and D-dimer assays. Another limitation was that differential verification biases for classifying fatal events and PE may have contributed to overestimation of failure rates of the adapted D-dimer thresholds.

Strengths of the study included its large sample size and original data on pretest probability, and that data support the use of any of the three strategies for ruling out PE in the identified subgroups without the need for imaging tests, the authors wrote.

“Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies,” they concluded.

Adapted D-dimer benefits some patients

“Clearly, increasing the D-dimer cutoff will lower the number of patients who require radiographic imaging (improved specificity), but this comes with a risk for missing PE (lower sensitivity). Is this risk worth taking?” Daniel J. Brotman, MD, of Johns Hopkins University, Baltimore, asked in an editorial accompanying the new study.

Dr. Brotman was not surprised by the study findings.

“Conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis,” he said. However, these patients are unlikely to have normal D-dimer levels regardless of the cutoff used.

Adapted D-dimer cutoffs may benefit some patients, including those with contraindications or limited access to imaging, said Dr. Brotman. D-dimer may be used for risk stratification regardless of PE, since patients with marginally elevated D-dimers have better prognoses than those with higher D-dimer elevations, even if a small PE is missed.

Dr. Brotman wrote that increasing D-dimer cutoffs for high-risk patients in the subgroups analyzed may spare some patients radiographic testing, but doing so carries an increased risk for diagnostic failure. Overall, “the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”
 

Focus on single strategy ‘based on local needs’

“Several validated clinical decision tools, along with age or pretest probability adjusted D-dimer threshold are currently in use as diagnostic strategies for ruling out pulmonary embolism,” Dr. Pal said in an interview.

The current study is important because of limited data on the performance of these strategies in specific subgroups of patients whose risk of PE may differ from the overall patient population, he noted.

“Different diagnostic strategies for PE have a variable performance in patients with differences of age, active cancer, and history of VTE,” said Dr. Pal. “However, in this study, no clear preference for one strategy over others could be established for these subgroups, and clinicians should continue to follow institution-specific guidance.

“A single strategy should be adopted at each institution based on local needs and used as the standard of care until further data are available,” he said.

“The use of D-dimer to rule out PE, either with fixed threshold or age-adjusted thresholds, can be confounded in clinical settings by other comorbid conditions such as sepsis, recent surgery, and more recently, COVID-19,” he said.

“Since the findings of this study do not show a clear benefit of one diagnostic strategy over others in the analyzed subgroups of patients, further prospective head-to-head comparison among the subgroups of interest would be helpful to guide clinical decision making,” Dr. Pal added.
 

YEARS-specific study supports D-dimer safety and value

A recent paper published in JAMA supported the results of the meta-analysis. In that study, Yonathan Freund, MD, of Sorbonne Université, Paris, and colleagues focused on the YEARS strategy combined with age-adjusted D-dimer thresholds as a way to rule out PE in PERC-positive ED patients.

The authors of this paper randomized 18 EDs to either a protocol of intervention followed by control, or control followed by intervention. The study population included 726 patients in the intervention group and 688 in the control group.

The intervention strategy to rule out PE consisted of assessing the YEARS criteria and D-dimer testing. PE was ruled out in patients with no YEARS criteria and a D-dimer level below 1,000 ng/mL and in patients with one or more YEARS criteria and D-dimers below an age-adjusted threshold (defined as age times 10 ng/mL in patients aged 50 years and older).

The control strategy consisted of D-dimer testing for all patients with the threshold at age-adjusted levels; D-dimers about these levels prompted chest imaging.

Overall, the risk of a missed VTE at 3 months was noninferior between the groups (0.15% in the intervention group and 0.80% in the controls).

“The intervention was associated with a statistically significant reduction in chest imaging use,” the researchers wrote.

This study’s findings were limited by randomization at the center level, rather than the patient level, and the use of imaging on some patients despite negative D-dimer tests, the researchers wrote. However, their findings support those of previous studies and especially support the safety of the intervention, in an emergency medicine setting, as no PEs occurred in patients with a YEARS score of zero who underwent the intervention.
 

Downsides to applying algorithms to every patient explained

In an editorial accompanying the JAMA study, Marcel Levi, MD, and Nick van Es, MD, of Amsterdam University Medical Center, emphasized the challenges of diagnosing PE given that many patients present with nonspecific clinical manifestations and without typical signs and symptoms. High-resolution CT pulmonary angiography allows for a fast and easy diagnosis in an emergency setting. However, efforts are ongoing to develop alternative strategies that avoid unnecessary scanning for potential PE patients, many of whom have alternative diagnoses such as pulmonary infections, cardiac conditions, pleural disease, or musculoskeletal problems.

On review of the JAMA study using the YEARS rule with adjusted D-dimer thresholds, the editorialists noted that the data were robust and indicated a 10% reduction in chest imaging. They also emphasized the potential to overwhelm busy clinicians with more algorithms.

“Blindly applying algorithms to every patient may be less appropriate or even undesirable in specific situations in which deviation from the rules on clinical grounds is indicated,” but a complex imaging approach may be time consuming and challenging in the acute setting, and a simple algorithm may be safe and efficient in many cases, they wrote. “From a patient perspective, a negative diagnostic algorithm for pulmonary embolism does not diminish the physician’s obligation to consider other diagnoses that explain the symptoms, for which chest CT scans may still be needed and helpful.”

The Annals of Internal Medicine study was supported by the Dutch Research Council. The JAMA study was supported by the French Health Ministry. Dr. Stals, Dr. Freund, Dr. Pal, Dr. Levi, and Dr. van Es had no financial conflicts to disclose.

Clinicians should approach decisions regarding coronary revascularization based on clinical indications without an eye toward sex, race, or ethnicity, advises a joint clinical practice guideline released Dec. 8 by the American Heart Association and American College of Cardiology.

The new class 1 recommendation leads off the 109-page document and reflects evidence demonstrating that revascularization is equally beneficial for all patients. Still, studies show that women and non-White patients are less likely to receive reperfusion therapy or revascularization.

“This was extremely important to all the committee members because of all of the disparities that have been documented not only in diagnosis but [in] the care provided to underrepresented minorities, women, and other ethnic groups,” said Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair.  

“We wanted to make it clear right at the beginning of the document that these guidelines apply to everyone, and we want it to be known that care should be the same for everyone,” she said in an interview.

The guideline was simultaneously published Dec. 9, 2021, in the journal  Circulation  and the  Journal of the American College of Cardiology. 

It updates and consolidates the ACC/AHA 2011 coronary artery bypass surgery (CABG) guideline and the ACC/AHA/Society for Cardiovascular Angiography and Interventions 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.

The new document emphasizes in a class 1 recommendation the importance of the multidisciplinary heart team in patients with coronary artery disease (CAD) where the best treatment strategy is unclear. But it also stresses that treatment decisions should be patient centered – taking into account patient preferences and goals, cultural beliefs, health literacy, and social determinants of cardiovascular health – and made in collaboration with the patient’s support system.

“Oftentimes we recommend a strategy of revascularization that may not be what the patient wants or hasn’t taken into account the patient’s preferences and also the family members,” Dr. Lawson said. “So we felt that was very important.”

Patients should also be provided with available evidence for various treatment options, including risks and benefits of each option, for informed consent. The two new class 1 recommendations are highlighted in a figure illustrating the shared decision-making algorithm that, by design, features a female clinician and Black patient.

“We spent 2 years debating the best revascularization strategies and we’re considered experts in the field – but when we talk to our patients, they really don’t know the benefits and risks,” she said. “In order to translate it to the layperson in basic terms, it’s important to say, ‘If you choose this option, you will likely live longer’ rather than using the jargon.”
 

DAPT, staged PCI, stable IHD

Among the top 10 take-home messages highlighted by the authors is a 2a recommendation that 1-3 months of dual antiplatelet therapy (DAPT) after PCI with a transition to P2Y12 inhibitor monotherapy is “reasonable” in selected patients to reduce the risk of bleeding events. Previous recommendations called for 6 or 12 months of DAPT.

enot-poloskun/Getty Images

“We really respect all of the clinical trials that came out showing that a shorter duration of DAPT is not inferior in terms of ischemic events but less bleeding, yet I don’t know how many clinicians are actually just using 3 months of DAPT followed by P2Y12 monotherapy,” guideline committee vice chair Jacqueline Tamis-Holland, MD, professor of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an interview. “So while it’s not a big, glaring giant recommendation, I think it will change a lot of practice.”

Similarly, she suggested that practice may shift as a result of a class 1 recommendation for staged PCI of a significantly stenosed nonculprit artery to reduce the risk for death or MI in selected hemodynamically stable patients presenting with ST-segment elevation MI and multivessel disease. “When you survey physicians, 75% of them do staged PCI but I think there will probably be more of an approach to staged PCI, as opposed to doing multivessel PCI at the time of primary PCI.”

Newer evidence from meta-analyses and the landmark ISCHEMIA trial showing no advantage of CABG over medical therapy in stable ischemic heart disease is reflected in a new class 2b recommendation – downgraded from class 1 in 2011 – that CABG “may be reasonable” to improve survival in stable patients with triple-vessel CAD.

The writing committee concluded that the ability of PCI to improve survival, compared with medical therapy in multivessel CAD “remains uncertain.”

Other recommendations likely to be of interest are that the radial artery is preferred, after the left internal mammary artery, as a surgical revascularization conduit over use of a saphenous vein conduit. Benefits include superior patency, fewer adverse cardiac events, and improved survival, the committee noted.

The radial artery is also recommended (class 1) in patients undergoing PCI who have acute coronary syndromes or stable ischemic heart disease to reduce bleeding and vascular complications compared with a femoral approach.

“Having both new radial recommendations sort of makes a bit of tension because the interventionalist is going to want to use the radial artery, but also the surgeon is too,” observed Dr. Tamis-Holland. “We see that in our own practice, so we try to have a collaborative approach to the patient to say: ‘Maybe do the cardiac cath in the dominant radial and then we can use the nondominant radial for a bypass conduit,’ but using both for each revascularization strategy will benefit the patient.

“So, we just have to remember that we’re going to talk together as a heart team and try to make the best decisions for each patient.”

A version of this article first appeared on Medscape.com.

Clinicians should approach decisions regarding coronary revascularization based on clinical indications without an eye toward sex, race, or ethnicity, advises a joint clinical practice guideline released Dec. 8 by the American Heart Association and American College of Cardiology.

The new class 1 recommendation leads off the 109-page document and reflects evidence demonstrating that revascularization is equally beneficial for all patients. Still, studies show that women and non-White patients are less likely to receive reperfusion therapy or revascularization.

“This was extremely important to all the committee members because of all of the disparities that have been documented not only in diagnosis but [in] the care provided to underrepresented minorities, women, and other ethnic groups,” said Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair.  

“We wanted to make it clear right at the beginning of the document that these guidelines apply to everyone, and we want it to be known that care should be the same for everyone,” she said in an interview.

The guideline was simultaneously published Dec. 9, 2021, in the journal  Circulation  and the  Journal of the American College of Cardiology. 

It updates and consolidates the ACC/AHA 2011 coronary artery bypass surgery (CABG) guideline and the ACC/AHA/Society for Cardiovascular Angiography and Interventions 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.

The new document emphasizes in a class 1 recommendation the importance of the multidisciplinary heart team in patients with coronary artery disease (CAD) where the best treatment strategy is unclear. But it also stresses that treatment decisions should be patient centered – taking into account patient preferences and goals, cultural beliefs, health literacy, and social determinants of cardiovascular health – and made in collaboration with the patient’s support system.

“Oftentimes we recommend a strategy of revascularization that may not be what the patient wants or hasn’t taken into account the patient’s preferences and also the family members,” Dr. Lawson said. “So we felt that was very important.”

Patients should also be provided with available evidence for various treatment options, including risks and benefits of each option, for informed consent. The two new class 1 recommendations are highlighted in a figure illustrating the shared decision-making algorithm that, by design, features a female clinician and Black patient.

“We spent 2 years debating the best revascularization strategies and we’re considered experts in the field – but when we talk to our patients, they really don’t know the benefits and risks,” she said. “In order to translate it to the layperson in basic terms, it’s important to say, ‘If you choose this option, you will likely live longer’ rather than using the jargon.”
 

DAPT, staged PCI, stable IHD

Among the top 10 take-home messages highlighted by the authors is a 2a recommendation that 1-3 months of dual antiplatelet therapy (DAPT) after PCI with a transition to P2Y12 inhibitor monotherapy is “reasonable” in selected patients to reduce the risk of bleeding events. Previous recommendations called for 6 or 12 months of DAPT.

enot-poloskun/Getty Images

“We really respect all of the clinical trials that came out showing that a shorter duration of DAPT is not inferior in terms of ischemic events but less bleeding, yet I don’t know how many clinicians are actually just using 3 months of DAPT followed by P2Y12 monotherapy,” guideline committee vice chair Jacqueline Tamis-Holland, MD, professor of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an interview. “So while it’s not a big, glaring giant recommendation, I think it will change a lot of practice.”

Similarly, she suggested that practice may shift as a result of a class 1 recommendation for staged PCI of a significantly stenosed nonculprit artery to reduce the risk for death or MI in selected hemodynamically stable patients presenting with ST-segment elevation MI and multivessel disease. “When you survey physicians, 75% of them do staged PCI but I think there will probably be more of an approach to staged PCI, as opposed to doing multivessel PCI at the time of primary PCI.”

Newer evidence from meta-analyses and the landmark ISCHEMIA trial showing no advantage of CABG over medical therapy in stable ischemic heart disease is reflected in a new class 2b recommendation – downgraded from class 1 in 2011 – that CABG “may be reasonable” to improve survival in stable patients with triple-vessel CAD.

The writing committee concluded that the ability of PCI to improve survival, compared with medical therapy in multivessel CAD “remains uncertain.”

Other recommendations likely to be of interest are that the radial artery is preferred, after the left internal mammary artery, as a surgical revascularization conduit over use of a saphenous vein conduit. Benefits include superior patency, fewer adverse cardiac events, and improved survival, the committee noted.

The radial artery is also recommended (class 1) in patients undergoing PCI who have acute coronary syndromes or stable ischemic heart disease to reduce bleeding and vascular complications compared with a femoral approach.

“Having both new radial recommendations sort of makes a bit of tension because the interventionalist is going to want to use the radial artery, but also the surgeon is too,” observed Dr. Tamis-Holland. “We see that in our own practice, so we try to have a collaborative approach to the patient to say: ‘Maybe do the cardiac cath in the dominant radial and then we can use the nondominant radial for a bypass conduit,’ but using both for each revascularization strategy will benefit the patient.

“So, we just have to remember that we’re going to talk together as a heart team and try to make the best decisions for each patient.”

A version of this article first appeared on Medscape.com.

Clinicians should approach decisions regarding coronary revascularization based on clinical indications without an eye toward sex, race, or ethnicity, advises a joint clinical practice guideline released Dec. 8 by the American Heart Association and American College of Cardiology.

The new class 1 recommendation leads off the 109-page document and reflects evidence demonstrating that revascularization is equally beneficial for all patients. Still, studies show that women and non-White patients are less likely to receive reperfusion therapy or revascularization.

“This was extremely important to all the committee members because of all of the disparities that have been documented not only in diagnosis but [in] the care provided to underrepresented minorities, women, and other ethnic groups,” said Jennifer S. Lawton, MD, chief of cardiac surgery at Johns Hopkins University, Baltimore, and guideline writing committee chair.  

“We wanted to make it clear right at the beginning of the document that these guidelines apply to everyone, and we want it to be known that care should be the same for everyone,” she said in an interview.

The guideline was simultaneously published Dec. 9, 2021, in the journal  Circulation  and the  Journal of the American College of Cardiology. 

It updates and consolidates the ACC/AHA 2011 coronary artery bypass surgery (CABG) guideline and the ACC/AHA/Society for Cardiovascular Angiography and Interventions 2011 and 2015 percutaneous coronary intervention (PCI) guidelines.

The new document emphasizes in a class 1 recommendation the importance of the multidisciplinary heart team in patients with coronary artery disease (CAD) where the best treatment strategy is unclear. But it also stresses that treatment decisions should be patient centered – taking into account patient preferences and goals, cultural beliefs, health literacy, and social determinants of cardiovascular health – and made in collaboration with the patient’s support system.

“Oftentimes we recommend a strategy of revascularization that may not be what the patient wants or hasn’t taken into account the patient’s preferences and also the family members,” Dr. Lawson said. “So we felt that was very important.”

Patients should also be provided with available evidence for various treatment options, including risks and benefits of each option, for informed consent. The two new class 1 recommendations are highlighted in a figure illustrating the shared decision-making algorithm that, by design, features a female clinician and Black patient.

“We spent 2 years debating the best revascularization strategies and we’re considered experts in the field – but when we talk to our patients, they really don’t know the benefits and risks,” she said. “In order to translate it to the layperson in basic terms, it’s important to say, ‘If you choose this option, you will likely live longer’ rather than using the jargon.”
 

DAPT, staged PCI, stable IHD

Among the top 10 take-home messages highlighted by the authors is a 2a recommendation that 1-3 months of dual antiplatelet therapy (DAPT) after PCI with a transition to P2Y12 inhibitor monotherapy is “reasonable” in selected patients to reduce the risk of bleeding events. Previous recommendations called for 6 or 12 months of DAPT.

enot-poloskun/Getty Images

“We really respect all of the clinical trials that came out showing that a shorter duration of DAPT is not inferior in terms of ischemic events but less bleeding, yet I don’t know how many clinicians are actually just using 3 months of DAPT followed by P2Y12 monotherapy,” guideline committee vice chair Jacqueline Tamis-Holland, MD, professor of medicine, Icahn School of Medicine at Mount Sinai, New York, said in an interview. “So while it’s not a big, glaring giant recommendation, I think it will change a lot of practice.”

Similarly, she suggested that practice may shift as a result of a class 1 recommendation for staged PCI of a significantly stenosed nonculprit artery to reduce the risk for death or MI in selected hemodynamically stable patients presenting with ST-segment elevation MI and multivessel disease. “When you survey physicians, 75% of them do staged PCI but I think there will probably be more of an approach to staged PCI, as opposed to doing multivessel PCI at the time of primary PCI.”

Newer evidence from meta-analyses and the landmark ISCHEMIA trial showing no advantage of CABG over medical therapy in stable ischemic heart disease is reflected in a new class 2b recommendation – downgraded from class 1 in 2011 – that CABG “may be reasonable” to improve survival in stable patients with triple-vessel CAD.

The writing committee concluded that the ability of PCI to improve survival, compared with medical therapy in multivessel CAD “remains uncertain.”

Other recommendations likely to be of interest are that the radial artery is preferred, after the left internal mammary artery, as a surgical revascularization conduit over use of a saphenous vein conduit. Benefits include superior patency, fewer adverse cardiac events, and improved survival, the committee noted.

The radial artery is also recommended (class 1) in patients undergoing PCI who have acute coronary syndromes or stable ischemic heart disease to reduce bleeding and vascular complications compared with a femoral approach.

“Having both new radial recommendations sort of makes a bit of tension because the interventionalist is going to want to use the radial artery, but also the surgeon is too,” observed Dr. Tamis-Holland. “We see that in our own practice, so we try to have a collaborative approach to the patient to say: ‘Maybe do the cardiac cath in the dominant radial and then we can use the nondominant radial for a bypass conduit,’ but using both for each revascularization strategy will benefit the patient.

“So, we just have to remember that we’re going to talk together as a heart team and try to make the best decisions for each patient.”

A version of this article first appeared on Medscape.com.

Background: DOACs have largely replaced VKAs as first-line therapy for venous thromboembolism in patients with adequate renal function. However, there is concern in APS that DOACs may have higher rates of recurrent thrombosis than VKAs when treating thromboembolism.

The DOAC arm was not proven to be noninferior with respect to the primary outcome of thrombotic events. The higher risk of stroke in this group suggests the need for caution in using DOACs in this population.

Bottom line: DOACs have a higher risk of stroke than VKAs in patients with APS without a significant difference in rate of a major bleed.

Citation: Ordi-Ros J et. al. Rivaroxaban versus vitamin K antagonist in antiphospholipid syndrome. Ann Intern Med. 2019;171(10):685-94. doi: 10.7326/M19-0291.

Dr. Portnoy is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: DOACs have largely replaced VKAs as first-line therapy for venous thromboembolism in patients with adequate renal function. However, there is concern in APS that DOACs may have higher rates of recurrent thrombosis than VKAs when treating thromboembolism.

The DOAC arm was not proven to be noninferior with respect to the primary outcome of thrombotic events. The higher risk of stroke in this group suggests the need for caution in using DOACs in this population.

Bottom line: DOACs have a higher risk of stroke than VKAs in patients with APS without a significant difference in rate of a major bleed.

Citation: Ordi-Ros J et. al. Rivaroxaban versus vitamin K antagonist in antiphospholipid syndrome. Ann Intern Med. 2019;171(10):685-94. doi: 10.7326/M19-0291.

Dr. Portnoy is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: DOACs have largely replaced VKAs as first-line therapy for venous thromboembolism in patients with adequate renal function. However, there is concern in APS that DOACs may have higher rates of recurrent thrombosis than VKAs when treating thromboembolism.

The DOAC arm was not proven to be noninferior with respect to the primary outcome of thrombotic events. The higher risk of stroke in this group suggests the need for caution in using DOACs in this population.

Bottom line: DOACs have a higher risk of stroke than VKAs in patients with APS without a significant difference in rate of a major bleed.

Citation: Ordi-Ros J et. al. Rivaroxaban versus vitamin K antagonist in antiphospholipid syndrome. Ann Intern Med. 2019;171(10):685-94. doi: 10.7326/M19-0291.

Dr. Portnoy is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: Over 6 million Americans are prescribed anticoagulation; however, available anticoagulation options for patients with concomitant renal impairment are limited. Until recently, warfarin was the only recommended option because of a lack of data to support the use of alternative agents in such patients. This study evaluates the safety and effectiveness of apixaban, compared with warfarin, in patients with severe renal dysfunction.

The main limitation is the retrospective observational design, which may have introduced confounding variables that were not accounted for in the analyses. The study also did not account for patient nonadherence to medication.

Bottom line: Apixaban is a reasonable alternative to warfarin in patients with severe renal impairment.

Citation: Hanni C et al. Outcomes associated with apixaban vs. warfarin in patients with renal dysfunction. Blood Adv. 2020;4(11): 2366-71. doi: 10.1182/bloodadvances.2019000972.

Dr. Narayan is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: Over 6 million Americans are prescribed anticoagulation; however, available anticoagulation options for patients with concomitant renal impairment are limited. Until recently, warfarin was the only recommended option because of a lack of data to support the use of alternative agents in such patients. This study evaluates the safety and effectiveness of apixaban, compared with warfarin, in patients with severe renal dysfunction.

The main limitation is the retrospective observational design, which may have introduced confounding variables that were not accounted for in the analyses. The study also did not account for patient nonadherence to medication.

Bottom line: Apixaban is a reasonable alternative to warfarin in patients with severe renal impairment.

Citation: Hanni C et al. Outcomes associated with apixaban vs. warfarin in patients with renal dysfunction. Blood Adv. 2020;4(11): 2366-71. doi: 10.1182/bloodadvances.2019000972.

Dr. Narayan is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: Over 6 million Americans are prescribed anticoagulation; however, available anticoagulation options for patients with concomitant renal impairment are limited. Until recently, warfarin was the only recommended option because of a lack of data to support the use of alternative agents in such patients. This study evaluates the safety and effectiveness of apixaban, compared with warfarin, in patients with severe renal dysfunction.

The main limitation is the retrospective observational design, which may have introduced confounding variables that were not accounted for in the analyses. The study also did not account for patient nonadherence to medication.

Bottom line: Apixaban is a reasonable alternative to warfarin in patients with severe renal impairment.

Citation: Hanni C et al. Outcomes associated with apixaban vs. warfarin in patients with renal dysfunction. Blood Adv. 2020;4(11): 2366-71. doi: 10.1182/bloodadvances.2019000972.

Dr. Narayan is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Apixaban appears to be safer and more effective than rivaroxaban for reducing risk of venous thromboembolism and bleeding, based on new research.

Recurrent venous thromboembolism (VTE) – a composite of pulmonary embolism and deep vein thrombosis – was the primary effectiveness outcome in the retrospective analysis of new-user data from almost 40,000 patients, which was published in Annals of Internal Medicine. Safety was evaluated through a composite of intracranial and gastrointestinal bleeding.

After a median follow-up of 102 days in the apixaban group and 105 days in the rivaroxaban group, apixaban demonstrated superiority for both primary outcomes.

These real-world findings may guide selection of initial anticoagulant therapy, reported lead author Ghadeer K. Dawwas, PhD, MSc, MBA, of the University of Pennsylvania, Philadelphia, and colleagues.

“Randomized clinical trials comparing apixaban with rivaroxaban in patients with VTE are under way (for example, COBRRA (NCT03266783),” the investigators wrote. “Until the results from these trials become available (The estimated completion date for COBRRA is December 2023.), observational studies that use existing data can provide evidence on the effectiveness and safety of these alternatives to inform clinical practice.”

In the new research, apixaban was associated with a 23% lower rate of recurrent VTE (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87), including a 15% lower rate of deep vein thrombosis and a 41% lower rate of pulmonary embolism. Apixaban was associated with 40% fewer bleeding events (HR, 0.60; 95% CI, 0.53-0.69]), including a 40% lower rate of GI bleeding and a 46% lower rate of intracranial bleeding.

The study involved 37,236 patients with VTE, all of whom were diagnosed in at least one inpatient encounter and initiated direct oral anticoagulant (DOAC) therapy within 30 days, according to Optum’s deidentified Clinformatics Data Mart Database. Patients were evenly split into apixaban and rivaroxaban groups, with 18,618 individuals in each. Propensity score matching was used to minimize differences in baseline characteristics.

Apixaban was associated with an absolute reduction in recurrent VTE of 0.6% and 1.1% over 2 and 6 months, respectively, as well as reductions in bleeding of 1.1% and 1.5% over the same respective time periods.

The investigators noted that these findings were maintained in various sensitivity and subgroup analyses, including a model in which patients with VTE who had transient risk factors were compared with VTE patients exhibiting chronic risk factors.

“These findings suggest that apixaban has superior effectiveness and safety, compared with rivaroxaban and may provide guidance to clinicians and patients regarding selection of an anticoagulant for treatment of VTE,” Dr. Dawwas and colleagues concluded.

Study may have missed some nuance in possible outcomes, according to vascular surgeon

Thomas Wakefield, MD, a vascular surgeon and a professor of surgery at the University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, generally agreed with the investigators’ conclusion, although he noted that DOAC selection may also be influenced by other considerations.

“The results of this study suggest that, when choosing an agent for an individual patient, apixaban does appear to have an advantage over rivaroxaban related to recurrent VTE and bleeding,” Dr. Wakefield said in an interview. “One must keep in mind that these are not the only factors that are considered when choosing an agent and these are not the only two DOACs available. For example, rivaroxaban is given once per day while apixaban is given twice per day, and rivaroxaban has been shown to be successful in the treatment of other thrombotic disorders.”

Dr. Wakefield also pointed out that the study may have missed some nuance in possible outcomes.

“The current study looked at severe outcomes that resulted in inpatient hospitalization, so the generalization to strictly outpatient treatment and less severe outcomes cannot be inferred,” he said.

Damon E. Houghton, MD, of the department of medicine and a consultant in the department of vascular medicine and hematology at Mayo Clinic, Rochester, Minn., called the study a “very nice analysis,” highlighting the large sample size.

“The results are not a reason to abandon rivaroxaban altogether, but do suggest that, when otherwise appropriate for a patient, apixaban should be the first choice,” Dr. Houghton said in a written comment. “Hopefully this analysis will encourage more payers to create financial incentives that facilitate the use of apixaban in more patients.”

Randomized trial needed, says hematologist

Colleen Edwards, MD, of the departments of medicine, hematology, and medical oncology, at the Icahn School of Medicine at Mount Sinai, New York, had a more guarded view of the findings than Dr. Wakefield and Dr. Houghton.

“[The investigators] certainly seem to be doing a lot of statistical gymnastics in this paper,” Dr. Edwards said in an interview. “They used all kinds of surrogates in place of real data that you would get from a randomized trial.”

For example, Dr. Edwards noted the use of prescription refills as a surrogate for medication adherence, and emphasized that inpatient observational data may not reflect outpatient therapy.

“Inpatients are constantly missing their medicines all the time,” she said. “They’re holding it for procedures, they’re NPO, they’re off the floor, so they missed their medicine. So it’s just a very different patient population than the outpatient population, which is where venous thromboembolism is treated now, by and large.”

Although Dr. Edwards suggested that the findings might guide treatment selection “a little bit,” she noted that insurance constraints and costs play a greater role, and ultimately concluded that a randomized trial is needed to materially alter clinical decision-making.

“I think we really have to wait for randomized trial before we abandon our other choices,” she said.

The investigators disclosed relationships with Merck, Celgene, UCB, and others. Dr. Wakefield reported awaiting disclosures. Dr. Houghton and Dr. Edwards reported no relevant conflicts of interest.

Apixaban appears to be safer and more effective than rivaroxaban for reducing risk of venous thromboembolism and bleeding, based on new research.

Recurrent venous thromboembolism (VTE) – a composite of pulmonary embolism and deep vein thrombosis – was the primary effectiveness outcome in the retrospective analysis of new-user data from almost 40,000 patients, which was published in Annals of Internal Medicine. Safety was evaluated through a composite of intracranial and gastrointestinal bleeding.

After a median follow-up of 102 days in the apixaban group and 105 days in the rivaroxaban group, apixaban demonstrated superiority for both primary outcomes.

These real-world findings may guide selection of initial anticoagulant therapy, reported lead author Ghadeer K. Dawwas, PhD, MSc, MBA, of the University of Pennsylvania, Philadelphia, and colleagues.

“Randomized clinical trials comparing apixaban with rivaroxaban in patients with VTE are under way (for example, COBRRA (NCT03266783),” the investigators wrote. “Until the results from these trials become available (The estimated completion date for COBRRA is December 2023.), observational studies that use existing data can provide evidence on the effectiveness and safety of these alternatives to inform clinical practice.”

In the new research, apixaban was associated with a 23% lower rate of recurrent VTE (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87), including a 15% lower rate of deep vein thrombosis and a 41% lower rate of pulmonary embolism. Apixaban was associated with 40% fewer bleeding events (HR, 0.60; 95% CI, 0.53-0.69]), including a 40% lower rate of GI bleeding and a 46% lower rate of intracranial bleeding.

The study involved 37,236 patients with VTE, all of whom were diagnosed in at least one inpatient encounter and initiated direct oral anticoagulant (DOAC) therapy within 30 days, according to Optum’s deidentified Clinformatics Data Mart Database. Patients were evenly split into apixaban and rivaroxaban groups, with 18,618 individuals in each. Propensity score matching was used to minimize differences in baseline characteristics.

Apixaban was associated with an absolute reduction in recurrent VTE of 0.6% and 1.1% over 2 and 6 months, respectively, as well as reductions in bleeding of 1.1% and 1.5% over the same respective time periods.

The investigators noted that these findings were maintained in various sensitivity and subgroup analyses, including a model in which patients with VTE who had transient risk factors were compared with VTE patients exhibiting chronic risk factors.

“These findings suggest that apixaban has superior effectiveness and safety, compared with rivaroxaban and may provide guidance to clinicians and patients regarding selection of an anticoagulant for treatment of VTE,” Dr. Dawwas and colleagues concluded.

Study may have missed some nuance in possible outcomes, according to vascular surgeon

Thomas Wakefield, MD, a vascular surgeon and a professor of surgery at the University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, generally agreed with the investigators’ conclusion, although he noted that DOAC selection may also be influenced by other considerations.

“The results of this study suggest that, when choosing an agent for an individual patient, apixaban does appear to have an advantage over rivaroxaban related to recurrent VTE and bleeding,” Dr. Wakefield said in an interview. “One must keep in mind that these are not the only factors that are considered when choosing an agent and these are not the only two DOACs available. For example, rivaroxaban is given once per day while apixaban is given twice per day, and rivaroxaban has been shown to be successful in the treatment of other thrombotic disorders.”

Dr. Wakefield also pointed out that the study may have missed some nuance in possible outcomes.

“The current study looked at severe outcomes that resulted in inpatient hospitalization, so the generalization to strictly outpatient treatment and less severe outcomes cannot be inferred,” he said.

Damon E. Houghton, MD, of the department of medicine and a consultant in the department of vascular medicine and hematology at Mayo Clinic, Rochester, Minn., called the study a “very nice analysis,” highlighting the large sample size.

“The results are not a reason to abandon rivaroxaban altogether, but do suggest that, when otherwise appropriate for a patient, apixaban should be the first choice,” Dr. Houghton said in a written comment. “Hopefully this analysis will encourage more payers to create financial incentives that facilitate the use of apixaban in more patients.”

Randomized trial needed, says hematologist

Colleen Edwards, MD, of the departments of medicine, hematology, and medical oncology, at the Icahn School of Medicine at Mount Sinai, New York, had a more guarded view of the findings than Dr. Wakefield and Dr. Houghton.

“[The investigators] certainly seem to be doing a lot of statistical gymnastics in this paper,” Dr. Edwards said in an interview. “They used all kinds of surrogates in place of real data that you would get from a randomized trial.”

For example, Dr. Edwards noted the use of prescription refills as a surrogate for medication adherence, and emphasized that inpatient observational data may not reflect outpatient therapy.

“Inpatients are constantly missing their medicines all the time,” she said. “They’re holding it for procedures, they’re NPO, they’re off the floor, so they missed their medicine. So it’s just a very different patient population than the outpatient population, which is where venous thromboembolism is treated now, by and large.”

Although Dr. Edwards suggested that the findings might guide treatment selection “a little bit,” she noted that insurance constraints and costs play a greater role, and ultimately concluded that a randomized trial is needed to materially alter clinical decision-making.

“I think we really have to wait for randomized trial before we abandon our other choices,” she said.

The investigators disclosed relationships with Merck, Celgene, UCB, and others. Dr. Wakefield reported awaiting disclosures. Dr. Houghton and Dr. Edwards reported no relevant conflicts of interest.

Apixaban appears to be safer and more effective than rivaroxaban for reducing risk of venous thromboembolism and bleeding, based on new research.

Recurrent venous thromboembolism (VTE) – a composite of pulmonary embolism and deep vein thrombosis – was the primary effectiveness outcome in the retrospective analysis of new-user data from almost 40,000 patients, which was published in Annals of Internal Medicine. Safety was evaluated through a composite of intracranial and gastrointestinal bleeding.

After a median follow-up of 102 days in the apixaban group and 105 days in the rivaroxaban group, apixaban demonstrated superiority for both primary outcomes.

These real-world findings may guide selection of initial anticoagulant therapy, reported lead author Ghadeer K. Dawwas, PhD, MSc, MBA, of the University of Pennsylvania, Philadelphia, and colleagues.

“Randomized clinical trials comparing apixaban with rivaroxaban in patients with VTE are under way (for example, COBRRA (NCT03266783),” the investigators wrote. “Until the results from these trials become available (The estimated completion date for COBRRA is December 2023.), observational studies that use existing data can provide evidence on the effectiveness and safety of these alternatives to inform clinical practice.”

In the new research, apixaban was associated with a 23% lower rate of recurrent VTE (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87), including a 15% lower rate of deep vein thrombosis and a 41% lower rate of pulmonary embolism. Apixaban was associated with 40% fewer bleeding events (HR, 0.60; 95% CI, 0.53-0.69]), including a 40% lower rate of GI bleeding and a 46% lower rate of intracranial bleeding.

The study involved 37,236 patients with VTE, all of whom were diagnosed in at least one inpatient encounter and initiated direct oral anticoagulant (DOAC) therapy within 30 days, according to Optum’s deidentified Clinformatics Data Mart Database. Patients were evenly split into apixaban and rivaroxaban groups, with 18,618 individuals in each. Propensity score matching was used to minimize differences in baseline characteristics.

Apixaban was associated with an absolute reduction in recurrent VTE of 0.6% and 1.1% over 2 and 6 months, respectively, as well as reductions in bleeding of 1.1% and 1.5% over the same respective time periods.

The investigators noted that these findings were maintained in various sensitivity and subgroup analyses, including a model in which patients with VTE who had transient risk factors were compared with VTE patients exhibiting chronic risk factors.

“These findings suggest that apixaban has superior effectiveness and safety, compared with rivaroxaban and may provide guidance to clinicians and patients regarding selection of an anticoagulant for treatment of VTE,” Dr. Dawwas and colleagues concluded.

Study may have missed some nuance in possible outcomes, according to vascular surgeon

Thomas Wakefield, MD, a vascular surgeon and a professor of surgery at the University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, generally agreed with the investigators’ conclusion, although he noted that DOAC selection may also be influenced by other considerations.

“The results of this study suggest that, when choosing an agent for an individual patient, apixaban does appear to have an advantage over rivaroxaban related to recurrent VTE and bleeding,” Dr. Wakefield said in an interview. “One must keep in mind that these are not the only factors that are considered when choosing an agent and these are not the only two DOACs available. For example, rivaroxaban is given once per day while apixaban is given twice per day, and rivaroxaban has been shown to be successful in the treatment of other thrombotic disorders.”

Dr. Wakefield also pointed out that the study may have missed some nuance in possible outcomes.

“The current study looked at severe outcomes that resulted in inpatient hospitalization, so the generalization to strictly outpatient treatment and less severe outcomes cannot be inferred,” he said.

Damon E. Houghton, MD, of the department of medicine and a consultant in the department of vascular medicine and hematology at Mayo Clinic, Rochester, Minn., called the study a “very nice analysis,” highlighting the large sample size.

“The results are not a reason to abandon rivaroxaban altogether, but do suggest that, when otherwise appropriate for a patient, apixaban should be the first choice,” Dr. Houghton said in a written comment. “Hopefully this analysis will encourage more payers to create financial incentives that facilitate the use of apixaban in more patients.”

Randomized trial needed, says hematologist

Colleen Edwards, MD, of the departments of medicine, hematology, and medical oncology, at the Icahn School of Medicine at Mount Sinai, New York, had a more guarded view of the findings than Dr. Wakefield and Dr. Houghton.

“[The investigators] certainly seem to be doing a lot of statistical gymnastics in this paper,” Dr. Edwards said in an interview. “They used all kinds of surrogates in place of real data that you would get from a randomized trial.”

For example, Dr. Edwards noted the use of prescription refills as a surrogate for medication adherence, and emphasized that inpatient observational data may not reflect outpatient therapy.

“Inpatients are constantly missing their medicines all the time,” she said. “They’re holding it for procedures, they’re NPO, they’re off the floor, so they missed their medicine. So it’s just a very different patient population than the outpatient population, which is where venous thromboembolism is treated now, by and large.”

Although Dr. Edwards suggested that the findings might guide treatment selection “a little bit,” she noted that insurance constraints and costs play a greater role, and ultimately concluded that a randomized trial is needed to materially alter clinical decision-making.

“I think we really have to wait for randomized trial before we abandon our other choices,” she said.

The investigators disclosed relationships with Merck, Celgene, UCB, and others. Dr. Wakefield reported awaiting disclosures. Dr. Houghton and Dr. Edwards reported no relevant conflicts of interest.

Background: VTE is common in patients with cancer and can lead to serious complications and death. Relatively recently, the use of edoxaban or rivaroxaban was recommended by major guidelines for the treatment of cancer-associated VTE. Previous studies have demonstrated a higher risk of major bleeding when compared with low-molecular-weight heparin. Whether oral apixaban can be safely used in this setting is unknown.

Dr. Hermansen is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: VTE is common in patients with cancer and can lead to serious complications and death. Relatively recently, the use of edoxaban or rivaroxaban was recommended by major guidelines for the treatment of cancer-associated VTE. Previous studies have demonstrated a higher risk of major bleeding when compared with low-molecular-weight heparin. Whether oral apixaban can be safely used in this setting is unknown.

Dr. Hermansen is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Background: VTE is common in patients with cancer and can lead to serious complications and death. Relatively recently, the use of edoxaban or rivaroxaban was recommended by major guidelines for the treatment of cancer-associated VTE. Previous studies have demonstrated a higher risk of major bleeding when compared with low-molecular-weight heparin. Whether oral apixaban can be safely used in this setting is unknown.

Dr. Hermansen is a hospitalist in the Division of Hospital Medicine, Mount Sinai Health System, New York.

Daily aspirin is associated with new onset heart failure independent of other risk factors, according to data derived from a database with follow-up from more than 30,000 patients who did not have HF when they were enrolled.

Patrice Wendling/MDedge News

These data are not relevant to primary or secondary prevention of cardiovascular events but “refer only to starting aspirin for secondary prevention of HF in patients at high risk of HF or with symptomatic HF,” according to the senior investigator, Jan A. Staessen, MD, PhD, professor emeritus at the University of Leuven (Belgium).

In data from 30,827 patients at risk for HF enrolled in six observational studies, the hazard ratio (HR) for developing HF among those taking daily aspirin at baseline relative to those who were not was 1.26 (P ≤ .001) over 5.3 years of follow-up. In the 22,690 patients without a prior history cardiovascular disease (CVD), the HF risk increase for exposure to daily aspirin was about the same (HR 1.27; P = .001).

This study was launched because multiple conflicting studies have made the relationship between aspirin and HF risk unclear, according to the multinational team of authors, whose finding were published in ESC Heart Failure.

In principle, HF is recognized as a prothrombotic condition for which an antithrombotic therapy such as aspirin would be expected to have a protective role, but the investigators pointed out that the evidence is mixed. In a population-based Danish study of 12,277 patients with new-onset HF, for example, there was no relationship seen between aspirin use and a reduction in the composite outcome of all-cause mortality, myocardial infarction, or stroke.

Aspirin use linked to HF admissions

“Interestingly, this study reported that aspirin use was associated with an increased risk of readmissions for HF,” wrote the authors of the newly published data. “Uncertainty on aspirin use has been reflected in current guideline recommendations,” they added.

The population studied was drawn from the HOMAGE database, which has collated data on 46,437 participants in 21 studies. After the exclusion of studies with patients who already had HF as well as studies without information on HF incidence over time, six studies with 30,827 participants provided the basis for this analysis.

One study, ASCOT, which was randomized and blinded, served as the derivation data set. The remaining five studies, FLEMENGHO, HEALTH ABC, HULL LIFE LAB, PREDICTOR, and PROSPER, served as the validation data set.

In addition to identifying participants as aspirin users or nonusers at baseline, all of the studies had detailed baseline data on a wide variety of patient characteristics and risk factors, such as body mass index, blood cholesterol levels, blood glucose concentrations, blood pressure, and creatinine.

No patient in any trial was on an antithrombotic therapy other than aspirin at baseline.

Of the minority of patients with CVD at baseline, more than 80% had coronary heart disease. Only 2.8% of the total population had a prior myocardial infarction. In the study population overall, most (86%) had hypertension, and there was a sizeable proportion with diabetes (22%). The average age was 67 years, and 34% were women.
 

HF incidence on aspirin: 14.5/1000 person-years

Overall, the incidence rate of HF per 1,000 person-years for the entire population before adjustment was 14.5 in the group on daily aspirin versus 5.9 in the non-aspirin group. These absolute rates were lower in the discovery data set than in the validation set, but the relative differences in HF incidence rates for those who were versus those who were not on aspirin at baseline were similar.

Numerous sensitivity analyses supported the basic conclusions. This not only included one omitting patients with a history of CVD, but another that excluded patients who developed HF within the first 2 years. Stratified analyses looking for overall consistency across variables showed increased risk of new onset heart failure among those taking daily aspirin regardless of relative age, body weight, or blood pressure levels.

The most important limitation of this study was that it evaluated data taken from studies not originally designed to test the study hypothesis. In addition, only baseline data were available, so the drugs that patients took over the course of follow-up are unknown. However, the authors believe these data have a clinical message.

Given the consistency of these results, “our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF,” the investigators concluded.

“If such treatment is initiated in these patients, use low-dose aspirin,” Dr. Staessen told this news organization.
 

Aspirin for CVD versus HF risk

Many patients take low-dose aspirin to prevent the types of cardiovascular events, such as MI, that lead to heart failure. In attempting to address a controversy regarding aspirin and risk of new onset heart failure, it appears to create another regarding CVD risk reduction.

Deepak L. Bhatt, MD, executive director of Interventional Cardiovascular Programs at Brigham and Women’s Health, Boston, expressed some reluctance in applying these data to routine practice.

“It is important to emphasize that this pooled analysis draws upon six observational studies, not randomized trials of aspirin,” Dr. Bhatt said.

He called these findings “provocative,” but he said they “would need to be confirmed in databases of already completed randomized trials of aspirin versus a control before being actionable.” For Dr. Bhatt, one obstacle to a change in practice based on these data is that, “to my knowledge, no such signal [of a relationship between aspirin and incident heart failure] exists in the cumulative randomized data.”

Dr. Staessen reports no potential conflicts of interest for this study. Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PLx Pharma, for which he performs aspirin-related research.
 

Daily aspirin is associated with new onset heart failure independent of other risk factors, according to data derived from a database with follow-up from more than 30,000 patients who did not have HF when they were enrolled.

Patrice Wendling/MDedge News

These data are not relevant to primary or secondary prevention of cardiovascular events but “refer only to starting aspirin for secondary prevention of HF in patients at high risk of HF or with symptomatic HF,” according to the senior investigator, Jan A. Staessen, MD, PhD, professor emeritus at the University of Leuven (Belgium).

In data from 30,827 patients at risk for HF enrolled in six observational studies, the hazard ratio (HR) for developing HF among those taking daily aspirin at baseline relative to those who were not was 1.26 (P ≤ .001) over 5.3 years of follow-up. In the 22,690 patients without a prior history cardiovascular disease (CVD), the HF risk increase for exposure to daily aspirin was about the same (HR 1.27; P = .001).

This study was launched because multiple conflicting studies have made the relationship between aspirin and HF risk unclear, according to the multinational team of authors, whose finding were published in ESC Heart Failure.

In principle, HF is recognized as a prothrombotic condition for which an antithrombotic therapy such as aspirin would be expected to have a protective role, but the investigators pointed out that the evidence is mixed. In a population-based Danish study of 12,277 patients with new-onset HF, for example, there was no relationship seen between aspirin use and a reduction in the composite outcome of all-cause mortality, myocardial infarction, or stroke.

Aspirin use linked to HF admissions

“Interestingly, this study reported that aspirin use was associated with an increased risk of readmissions for HF,” wrote the authors of the newly published data. “Uncertainty on aspirin use has been reflected in current guideline recommendations,” they added.

The population studied was drawn from the HOMAGE database, which has collated data on 46,437 participants in 21 studies. After the exclusion of studies with patients who already had HF as well as studies without information on HF incidence over time, six studies with 30,827 participants provided the basis for this analysis.

One study, ASCOT, which was randomized and blinded, served as the derivation data set. The remaining five studies, FLEMENGHO, HEALTH ABC, HULL LIFE LAB, PREDICTOR, and PROSPER, served as the validation data set.

In addition to identifying participants as aspirin users or nonusers at baseline, all of the studies had detailed baseline data on a wide variety of patient characteristics and risk factors, such as body mass index, blood cholesterol levels, blood glucose concentrations, blood pressure, and creatinine.

No patient in any trial was on an antithrombotic therapy other than aspirin at baseline.

Of the minority of patients with CVD at baseline, more than 80% had coronary heart disease. Only 2.8% of the total population had a prior myocardial infarction. In the study population overall, most (86%) had hypertension, and there was a sizeable proportion with diabetes (22%). The average age was 67 years, and 34% were women.
 

HF incidence on aspirin: 14.5/1000 person-years

Overall, the incidence rate of HF per 1,000 person-years for the entire population before adjustment was 14.5 in the group on daily aspirin versus 5.9 in the non-aspirin group. These absolute rates were lower in the discovery data set than in the validation set, but the relative differences in HF incidence rates for those who were versus those who were not on aspirin at baseline were similar.

Numerous sensitivity analyses supported the basic conclusions. This not only included one omitting patients with a history of CVD, but another that excluded patients who developed HF within the first 2 years. Stratified analyses looking for overall consistency across variables showed increased risk of new onset heart failure among those taking daily aspirin regardless of relative age, body weight, or blood pressure levels.

The most important limitation of this study was that it evaluated data taken from studies not originally designed to test the study hypothesis. In addition, only baseline data were available, so the drugs that patients took over the course of follow-up are unknown. However, the authors believe these data have a clinical message.

Given the consistency of these results, “our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF,” the investigators concluded.

“If such treatment is initiated in these patients, use low-dose aspirin,” Dr. Staessen told this news organization.
 

Aspirin for CVD versus HF risk

Many patients take low-dose aspirin to prevent the types of cardiovascular events, such as MI, that lead to heart failure. In attempting to address a controversy regarding aspirin and risk of new onset heart failure, it appears to create another regarding CVD risk reduction.

Deepak L. Bhatt, MD, executive director of Interventional Cardiovascular Programs at Brigham and Women’s Health, Boston, expressed some reluctance in applying these data to routine practice.

“It is important to emphasize that this pooled analysis draws upon six observational studies, not randomized trials of aspirin,” Dr. Bhatt said.

He called these findings “provocative,” but he said they “would need to be confirmed in databases of already completed randomized trials of aspirin versus a control before being actionable.” For Dr. Bhatt, one obstacle to a change in practice based on these data is that, “to my knowledge, no such signal [of a relationship between aspirin and incident heart failure] exists in the cumulative randomized data.”

Dr. Staessen reports no potential conflicts of interest for this study. Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PLx Pharma, for which he performs aspirin-related research.
 

Daily aspirin is associated with new onset heart failure independent of other risk factors, according to data derived from a database with follow-up from more than 30,000 patients who did not have HF when they were enrolled.

Patrice Wendling/MDedge News

These data are not relevant to primary or secondary prevention of cardiovascular events but “refer only to starting aspirin for secondary prevention of HF in patients at high risk of HF or with symptomatic HF,” according to the senior investigator, Jan A. Staessen, MD, PhD, professor emeritus at the University of Leuven (Belgium).

In data from 30,827 patients at risk for HF enrolled in six observational studies, the hazard ratio (HR) for developing HF among those taking daily aspirin at baseline relative to those who were not was 1.26 (P ≤ .001) over 5.3 years of follow-up. In the 22,690 patients without a prior history cardiovascular disease (CVD), the HF risk increase for exposure to daily aspirin was about the same (HR 1.27; P = .001).

This study was launched because multiple conflicting studies have made the relationship between aspirin and HF risk unclear, according to the multinational team of authors, whose finding were published in ESC Heart Failure.

In principle, HF is recognized as a prothrombotic condition for which an antithrombotic therapy such as aspirin would be expected to have a protective role, but the investigators pointed out that the evidence is mixed. In a population-based Danish study of 12,277 patients with new-onset HF, for example, there was no relationship seen between aspirin use and a reduction in the composite outcome of all-cause mortality, myocardial infarction, or stroke.

Aspirin use linked to HF admissions

“Interestingly, this study reported that aspirin use was associated with an increased risk of readmissions for HF,” wrote the authors of the newly published data. “Uncertainty on aspirin use has been reflected in current guideline recommendations,” they added.

The population studied was drawn from the HOMAGE database, which has collated data on 46,437 participants in 21 studies. After the exclusion of studies with patients who already had HF as well as studies without information on HF incidence over time, six studies with 30,827 participants provided the basis for this analysis.

One study, ASCOT, which was randomized and blinded, served as the derivation data set. The remaining five studies, FLEMENGHO, HEALTH ABC, HULL LIFE LAB, PREDICTOR, and PROSPER, served as the validation data set.

In addition to identifying participants as aspirin users or nonusers at baseline, all of the studies had detailed baseline data on a wide variety of patient characteristics and risk factors, such as body mass index, blood cholesterol levels, blood glucose concentrations, blood pressure, and creatinine.

No patient in any trial was on an antithrombotic therapy other than aspirin at baseline.

Of the minority of patients with CVD at baseline, more than 80% had coronary heart disease. Only 2.8% of the total population had a prior myocardial infarction. In the study population overall, most (86%) had hypertension, and there was a sizeable proportion with diabetes (22%). The average age was 67 years, and 34% were women.
 

HF incidence on aspirin: 14.5/1000 person-years

Overall, the incidence rate of HF per 1,000 person-years for the entire population before adjustment was 14.5 in the group on daily aspirin versus 5.9 in the non-aspirin group. These absolute rates were lower in the discovery data set than in the validation set, but the relative differences in HF incidence rates for those who were versus those who were not on aspirin at baseline were similar.

Numerous sensitivity analyses supported the basic conclusions. This not only included one omitting patients with a history of CVD, but another that excluded patients who developed HF within the first 2 years. Stratified analyses looking for overall consistency across variables showed increased risk of new onset heart failure among those taking daily aspirin regardless of relative age, body weight, or blood pressure levels.

The most important limitation of this study was that it evaluated data taken from studies not originally designed to test the study hypothesis. In addition, only baseline data were available, so the drugs that patients took over the course of follow-up are unknown. However, the authors believe these data have a clinical message.

Given the consistency of these results, “our observations suggest that aspirin should be prescribed with caution in patients at risk of HF or having HF,” the investigators concluded.

“If such treatment is initiated in these patients, use low-dose aspirin,” Dr. Staessen told this news organization.
 

Aspirin for CVD versus HF risk

Many patients take low-dose aspirin to prevent the types of cardiovascular events, such as MI, that lead to heart failure. In attempting to address a controversy regarding aspirin and risk of new onset heart failure, it appears to create another regarding CVD risk reduction.

Deepak L. Bhatt, MD, executive director of Interventional Cardiovascular Programs at Brigham and Women’s Health, Boston, expressed some reluctance in applying these data to routine practice.

“It is important to emphasize that this pooled analysis draws upon six observational studies, not randomized trials of aspirin,” Dr. Bhatt said.

He called these findings “provocative,” but he said they “would need to be confirmed in databases of already completed randomized trials of aspirin versus a control before being actionable.” For Dr. Bhatt, one obstacle to a change in practice based on these data is that, “to my knowledge, no such signal [of a relationship between aspirin and incident heart failure] exists in the cumulative randomized data.”

Dr. Staessen reports no potential conflicts of interest for this study. Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PLx Pharma, for which he performs aspirin-related research.
 

The experimental monoclonal antibody bentracimab, which reverses the antiplatelet effects of ticagrelor, appears to be heading toward regulatory approval, on the basis of an interim analysis of the phase 3 REVERSE-IT trial.

“Rates of effective hemostasis were adjudicated as good or excellent in more than 90% of cases with no drug-related serious adverse events or allergic or infusion-related reactions,” reported Deepak L. Bhatt, MD, at the American Heart Association scientific sessions.

The interim analysis of this nonrandomized, single-arm study was requested by the Food and Drug Administration, which is considering a conditional accelerated approval of bentracimab (formerly PB2452) if efficacy and safety are established.

Upon administration, bentracimab binds to free ticagrelor so that ticagrelor cannot bind to the P2Y12 platelet receptor. This interrupts one of the key steps in the pathway of platelet aggregation.

REVERSE-IT is still enrolling patients. This interim analysis was conducted with the first 150 patients who met eligibility criteria and were treated. Of these, 142 patients were enrolled for an urgent surgical indication and 8 for a major bleeding indication. After some exclusions for lack of urgency and reclassifications following adjudication, there were 113 surgical cases and 9 major bleeding patients evaluable for hemostasis.
 

Platelet function assays test reversal

On the primary reversal endpoint, which was restoration of activity on the proprietary platelet function assays Verify Now and PRUTest, a rapid restoration of platelet function was achieved in both surgical and major-bleeding patients. Platelet reactivity climbed to near normal levels within 10 minutes of administration, and peak effects were sustained through the first 24 hours after administration.

On the basis of the platelet function assays, the pattern of response to bentracimab was “very similar in the surgical and bleeding patients,” reported Dr. Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Health, Boston.

The effect was also consistent across a broad array of prespecified subgroups, including stratifications by age, renal function, time from last dose of ticagrelor, race, and the presence of comorbidities, such as diabetes, renal dysfunction, hypertension, and history of MI.
 

Hemostasis documented in all but one patient

Adjudicated hemostasis was achieved in 100% of the 113 urgent surgical patients evaluated. In the nine major bleeding patients, six achieved excellent hemostasis and one achieved good hemostasis. One had poor hemostasis, and one was unevaluable.

Platelet rebound following bentracimab administration, measured by mean platelet volume, was not observed.

There were no serious adverse events, allergic reactions, or serious infusion-related reactions associated with the administration of bentracimab, Dr. Bhatt said.

While Dr. Bhatt acknowledged that the number of patients in the major-bleeding subgroup was small, he noted that the reduction in platelet reactivity relative to baseline was still significant. In addition, he characterized urgent surgery as “an excellent model of bleeding” and pointed out the consistency of results in the surgical and major-bleeding groups.

The interim results are also consistent with phase 1 data published 2 years ago, and with the subsequent phase 2 studies. All of these data are now under regulatory review both in the United States and in Europe, according to Dr. Bhatt.
 

No good current options for reversal

Evidence of efficacy and safety is encouraging, because current options for urgently reversing ticagrelor are “disappointing,” according to the invited discussant Gilles Montalescot, MD, PhD, professor of cardiology, Pitié-Salpêtrière Hôpital, Paris.

“Platelet transfusion has some value for clopidogrel and prasugrel, but it does not work for ticagrelor,” said Dr. Montalescot, referring to two other P2Y12 inhibitors. Substantiating the need for a reversal agent, he identified several other strategies that have proven ineffective, such as desmopressin and sorbent hemadsorption.

Overall, Dr. Montalescot acknowledged the need for a highly effective ticagrelor reversal agent, but he did have some criticisms of REVERSE-IT. For one, he was not convinced about the design.

“What was unethical in having a control group?” he asked, suggesting that it was feasible and would have addressed issues of relative efficacy and safety.

For example, the authors concluded that none of the thrombotic events were likely to be treatment related, but “four events occurred immediately after reversal without an alternate explanation,” Dr. Montalescot pointed out. “Was this a signal or background noise?”

Nevertheless, he agreed that the interim phase 3 data are consistent with the previously reported phase 2 studies, and he reiterated that a strategy to reverse ticagrelor’s effects is an important unmet need.

Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PhaseBio, which provided funding for the REVERSE-IT trial. Dr. Montalescot reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cell-Prothera, CSL-Behring, Europa, Idorsia, Servicer, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.
 

The experimental monoclonal antibody bentracimab, which reverses the antiplatelet effects of ticagrelor, appears to be heading toward regulatory approval, on the basis of an interim analysis of the phase 3 REVERSE-IT trial.

“Rates of effective hemostasis were adjudicated as good or excellent in more than 90% of cases with no drug-related serious adverse events or allergic or infusion-related reactions,” reported Deepak L. Bhatt, MD, at the American Heart Association scientific sessions.

The interim analysis of this nonrandomized, single-arm study was requested by the Food and Drug Administration, which is considering a conditional accelerated approval of bentracimab (formerly PB2452) if efficacy and safety are established.

Upon administration, bentracimab binds to free ticagrelor so that ticagrelor cannot bind to the P2Y12 platelet receptor. This interrupts one of the key steps in the pathway of platelet aggregation.

REVERSE-IT is still enrolling patients. This interim analysis was conducted with the first 150 patients who met eligibility criteria and were treated. Of these, 142 patients were enrolled for an urgent surgical indication and 8 for a major bleeding indication. After some exclusions for lack of urgency and reclassifications following adjudication, there were 113 surgical cases and 9 major bleeding patients evaluable for hemostasis.
 

Platelet function assays test reversal

On the primary reversal endpoint, which was restoration of activity on the proprietary platelet function assays Verify Now and PRUTest, a rapid restoration of platelet function was achieved in both surgical and major-bleeding patients. Platelet reactivity climbed to near normal levels within 10 minutes of administration, and peak effects were sustained through the first 24 hours after administration.

On the basis of the platelet function assays, the pattern of response to bentracimab was “very similar in the surgical and bleeding patients,” reported Dr. Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Health, Boston.

The effect was also consistent across a broad array of prespecified subgroups, including stratifications by age, renal function, time from last dose of ticagrelor, race, and the presence of comorbidities, such as diabetes, renal dysfunction, hypertension, and history of MI.
 

Hemostasis documented in all but one patient

Adjudicated hemostasis was achieved in 100% of the 113 urgent surgical patients evaluated. In the nine major bleeding patients, six achieved excellent hemostasis and one achieved good hemostasis. One had poor hemostasis, and one was unevaluable.

Platelet rebound following bentracimab administration, measured by mean platelet volume, was not observed.

There were no serious adverse events, allergic reactions, or serious infusion-related reactions associated with the administration of bentracimab, Dr. Bhatt said.

While Dr. Bhatt acknowledged that the number of patients in the major-bleeding subgroup was small, he noted that the reduction in platelet reactivity relative to baseline was still significant. In addition, he characterized urgent surgery as “an excellent model of bleeding” and pointed out the consistency of results in the surgical and major-bleeding groups.

The interim results are also consistent with phase 1 data published 2 years ago, and with the subsequent phase 2 studies. All of these data are now under regulatory review both in the United States and in Europe, according to Dr. Bhatt.
 

No good current options for reversal

Evidence of efficacy and safety is encouraging, because current options for urgently reversing ticagrelor are “disappointing,” according to the invited discussant Gilles Montalescot, MD, PhD, professor of cardiology, Pitié-Salpêtrière Hôpital, Paris.

“Platelet transfusion has some value for clopidogrel and prasugrel, but it does not work for ticagrelor,” said Dr. Montalescot, referring to two other P2Y12 inhibitors. Substantiating the need for a reversal agent, he identified several other strategies that have proven ineffective, such as desmopressin and sorbent hemadsorption.

Overall, Dr. Montalescot acknowledged the need for a highly effective ticagrelor reversal agent, but he did have some criticisms of REVERSE-IT. For one, he was not convinced about the design.

“What was unethical in having a control group?” he asked, suggesting that it was feasible and would have addressed issues of relative efficacy and safety.

For example, the authors concluded that none of the thrombotic events were likely to be treatment related, but “four events occurred immediately after reversal without an alternate explanation,” Dr. Montalescot pointed out. “Was this a signal or background noise?”

Nevertheless, he agreed that the interim phase 3 data are consistent with the previously reported phase 2 studies, and he reiterated that a strategy to reverse ticagrelor’s effects is an important unmet need.

Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PhaseBio, which provided funding for the REVERSE-IT trial. Dr. Montalescot reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cell-Prothera, CSL-Behring, Europa, Idorsia, Servicer, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.
 

The experimental monoclonal antibody bentracimab, which reverses the antiplatelet effects of ticagrelor, appears to be heading toward regulatory approval, on the basis of an interim analysis of the phase 3 REVERSE-IT trial.

“Rates of effective hemostasis were adjudicated as good or excellent in more than 90% of cases with no drug-related serious adverse events or allergic or infusion-related reactions,” reported Deepak L. Bhatt, MD, at the American Heart Association scientific sessions.

The interim analysis of this nonrandomized, single-arm study was requested by the Food and Drug Administration, which is considering a conditional accelerated approval of bentracimab (formerly PB2452) if efficacy and safety are established.

Upon administration, bentracimab binds to free ticagrelor so that ticagrelor cannot bind to the P2Y12 platelet receptor. This interrupts one of the key steps in the pathway of platelet aggregation.

REVERSE-IT is still enrolling patients. This interim analysis was conducted with the first 150 patients who met eligibility criteria and were treated. Of these, 142 patients were enrolled for an urgent surgical indication and 8 for a major bleeding indication. After some exclusions for lack of urgency and reclassifications following adjudication, there were 113 surgical cases and 9 major bleeding patients evaluable for hemostasis.
 

Platelet function assays test reversal

On the primary reversal endpoint, which was restoration of activity on the proprietary platelet function assays Verify Now and PRUTest, a rapid restoration of platelet function was achieved in both surgical and major-bleeding patients. Platelet reactivity climbed to near normal levels within 10 minutes of administration, and peak effects were sustained through the first 24 hours after administration.

On the basis of the platelet function assays, the pattern of response to bentracimab was “very similar in the surgical and bleeding patients,” reported Dr. Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Health, Boston.

The effect was also consistent across a broad array of prespecified subgroups, including stratifications by age, renal function, time from last dose of ticagrelor, race, and the presence of comorbidities, such as diabetes, renal dysfunction, hypertension, and history of MI.
 

Hemostasis documented in all but one patient

Adjudicated hemostasis was achieved in 100% of the 113 urgent surgical patients evaluated. In the nine major bleeding patients, six achieved excellent hemostasis and one achieved good hemostasis. One had poor hemostasis, and one was unevaluable.

Platelet rebound following bentracimab administration, measured by mean platelet volume, was not observed.

There were no serious adverse events, allergic reactions, or serious infusion-related reactions associated with the administration of bentracimab, Dr. Bhatt said.

While Dr. Bhatt acknowledged that the number of patients in the major-bleeding subgroup was small, he noted that the reduction in platelet reactivity relative to baseline was still significant. In addition, he characterized urgent surgery as “an excellent model of bleeding” and pointed out the consistency of results in the surgical and major-bleeding groups.

The interim results are also consistent with phase 1 data published 2 years ago, and with the subsequent phase 2 studies. All of these data are now under regulatory review both in the United States and in Europe, according to Dr. Bhatt.
 

No good current options for reversal

Evidence of efficacy and safety is encouraging, because current options for urgently reversing ticagrelor are “disappointing,” according to the invited discussant Gilles Montalescot, MD, PhD, professor of cardiology, Pitié-Salpêtrière Hôpital, Paris.

“Platelet transfusion has some value for clopidogrel and prasugrel, but it does not work for ticagrelor,” said Dr. Montalescot, referring to two other P2Y12 inhibitors. Substantiating the need for a reversal agent, he identified several other strategies that have proven ineffective, such as desmopressin and sorbent hemadsorption.

Overall, Dr. Montalescot acknowledged the need for a highly effective ticagrelor reversal agent, but he did have some criticisms of REVERSE-IT. For one, he was not convinced about the design.

“What was unethical in having a control group?” he asked, suggesting that it was feasible and would have addressed issues of relative efficacy and safety.

For example, the authors concluded that none of the thrombotic events were likely to be treatment related, but “four events occurred immediately after reversal without an alternate explanation,” Dr. Montalescot pointed out. “Was this a signal or background noise?”

Nevertheless, he agreed that the interim phase 3 data are consistent with the previously reported phase 2 studies, and he reiterated that a strategy to reverse ticagrelor’s effects is an important unmet need.

Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PhaseBio, which provided funding for the REVERSE-IT trial. Dr. Montalescot reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cell-Prothera, CSL-Behring, Europa, Idorsia, Servicer, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.
 

Breast cancer treatment often results in shoulder and arm problems, such as chronic pain, restricted shoulder movement, or lymphedema in the armpit area, limiting quality of life and delaying recovery. However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.

“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.

Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.

“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.

In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.

At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.

“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”

While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.

“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.

The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.

Breast cancer treatment often results in shoulder and arm problems, such as chronic pain, restricted shoulder movement, or lymphedema in the armpit area, limiting quality of life and delaying recovery. However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.

“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.

Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.

“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.

In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.

At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.

“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”

While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.

“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.

The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.

Breast cancer treatment often results in shoulder and arm problems, such as chronic pain, restricted shoulder movement, or lymphedema in the armpit area, limiting quality of life and delaying recovery. However, according to a U.K. study published by The BMJ on Nov. 10, women who exercised shortly after having nonreconstructive breast cancer surgery experienced less pain and regained better shoulder and arm mobility at 1 year than those who did not exercise.

“Hospitals should consider training physiotherapists in the PROSPER program to offer this structured, prescribed exercise program to women undergoing axillary clearance surgery and those having radiotherapy to the axilla,” said lead author Julie Bruce, PhD, a specialist in surgical epidemiology with the University of Warwick, Coventry, England.

Up to one-third of women experience adverse effects to their lymphatic and musculoskeletal systems after breast cancer surgery and radiotherapy targeting the axilla. A study of 2,411 women in Denmark found that pain remained for up to 7 years after breast cancer treatment. U.K. guidelines for the management of breast cancer recommend referral to physical therapy if such problems develop, but the best timing and intensity along with the safety of postoperative exercise remain uncertain. A review of the literature in 2019 found a lack of adequate evidence to support the use of postoperative exercise after breast cancer surgery. Moreover, concerns with such exercise have been reported, such as increased risks of postoperative wound complications and lymphedema.

“The study was conducted to address uncertainty whether early postoperative exercise after women at high risk of shoulder and arm problems after nonreconstructive surgery was safe, clinically, and cost-effective. Previous studies were small, and no large high-quality randomized controlled trials had been undertaken with this patient population in the U.K.,” Dr. Bruce said.

In UK PROSPER, a multicenter, randomized controlled trial, researchers investigated the effects of an exercise program compared with usual care for 392 women (mean age 58) undergoing breast cancer surgery at 17 National Health Service (NHS) cancer centers. The women were randomly assigned to usual care with structured exercise or usual care alone. Structured exercise, introduced 7-10 days postoperatively, consisted of a physical therapy–led exercise program comprising stretching, strengthening, and physical activity, along with behavioral change techniques to support exercise adherence. Two further appointments were offered 1 and 3 months later. Outcomes included upper limb function, as measured by the Disability of Arm, Hand, and Shoulder (DASH) questionnaire at 12 months, complications, health related quality of life, and cost effectiveness.

At 12 months, women in the exercise group showed improved upper limb function compared with those who received usual care (mean DASH 16.3 for exercise, 23.7 for usual care; adjusted mean difference 7.81, 95% confidence interval, 3.17-12.44; P = .001). Compared with the usual care group, women in the exercise group reported lower pain intensity, fewer arm disability symptoms, and better health related quality of life.

“We found that arm function, measured using the DASH scale, improved over time and found surprisingly, these differences between treatment groups persisted at 12 months,” Dr. Bruce said. “There was no increased risk of neuropathic pain or lymphedema, so we concluded that the structured exercise program introduced from the seventh postoperative day was safe. Strengthening exercises were introduced from 1 month postoperatively.”

While the authors noted that the study was limited as participants and physical therapists knew which treatment they were receiving, they stressed that the study included a larger sample size than that of previous trials, along with a long follow-up period.

“We know that some women develop late lymphedema. Our findings are based on follow-up at 12 months. We hope to undertake longer-term follow up of our patient sample in the future,” Dr. Bruce said.

The authors declared support from the UK National Institute for Health Research (NIHR) Technology Assessment Programme.

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Extended follow-up of the PRAGUE-17 trial suggests left atrial appendage closure (LAAC) remains noninferior to direct-acting oral anticoagulants (DOACs) with regard to major cardiovascular and neurologic events in high-risk patients with atrial fibrillation.

At a median follow-up of 3.5 years, the annualized rate of the primary outcome – a composite of stroke, transient ischemic attack (TIA), systemic embolism, cardiovascular death, clinically relevant bleeding, or significant procedure- or device-related complications – was 8.6% in patients who underwent LAAC and 11.9% in those managed with DOACs (P value for noninferiority = .006).

The study was not powered to assess the individual components, but most were similar between the LAAC and DOAC groups, including cardiovascular death (20 vs. 30 events) and all stroke/TIA (16 vs. 18 events).

Nonprocedural clinically relevant bleeding was lower with LAAC (23 vs. 40 events; annualized rate, 3.4% vs. 5.9%; P = .039), said Pavel Osmancik, MD, PhD, Charles University and University Hospital Kralovske Vinohrady, both in Prague.

The data were presented at the Transcatheter Cardiovascular Therapeutics annual meeting, held virtually and live in Orlando and sponsored by the Cardiovascular Research Foundation, and was published simultaneously in the Journal of the American College of Cardiology.

The results are generally in line with those reported in 2020 with an average follow-up of 20 months, when the annualized primary event rate was 11% with LAAC and 13% with DOACs, also known as novel OACs (NOACs).

The trial randomly assigned 415 patients to LAAC with the Amulet (Abbott Vascular) or Watchman/Watchman FLX devices (Boston Scientific) or to rivaroxaban, dabigatran, or preferably apixaban (96%). The modified intention-to-treat analysis included 201 patients in each group, with follow-up extending to 4.3 years in the LAAC group and 4.2 years in the DOAC group.

Dr. Osmancik said the trial enrolled a very-high-risk atrial fibrillation cohort, citing a CHA2DS2-VASc score of 4.7 in both groups and a HAS-BLED score of 3.0-3.1. More than half of the LAAC group (54.2%) and 47.3% of the DOAC group had a history of bleeding or bleeding predisposition.

During a discussion of the results, the panel questioned whether the continuing divergence of the primary event curves at 4 years was potentially related to the effect of noncompliance to the NOACs over time.

Dr. Osmancik replied: “We didn’t do any medication look among the patients, but I don’t think that the number of patients who stopped the NOAC treatment was too high because the rate of strokes was very similar to that in the NOAC trials.”

He reported that 26 patients in the DOAC group permanently stopped their DOAC during follow-up; 15 (58%) because of clinically relevant bleeding, and 13 crossed over to LAAC. Of the 13 patients, 12 cases were successful with dual antiplatelet therapy for 3 months.

In the LAAC group, 17 patients started a DOAC during follow-up. Of these, three (18%) initiated DOAC treatment because of device-related thrombus (DRT) on transesophageal echocardiography, three (18%) because of a peridevice leak (PDL), and five (29%) because of a stroke/TIA.

“Given the observed trend of significantly increased nonprocedural clinically relevant bleeding in the NOAC arm, it is likely that late bleeding events will increasingly favor LAAC over time,” Faisal Merchant, MD, Emory University, Atlanta, wrote in an accompanying editorial.

NOACs, he noted, have important indications beyond prevention of left atrial appendage thrombi, including prevention of non-LAA sources of stroke/systemic embolism (SSE) and treatment of venous thromboembolism. “If significant numbers of patients treated with LAAC end up on anticoagulation in the long run, the benefits of LAAC are likely to be attenuated.”

Although PRAGUE-17 provides some insights into the longer-term indications for resuming anticoagulation in patients previously treated with LAAC, Dr. Merchant said the trial is a “real missed opportunity” in terms of understanding late device-associated risks. Unfortunately, two-thirds of the follow-up transesophageal echocardiograms were canceled because of the COVID-19 pandemic.

“Although the incidence of late DRT and PDL isn’t known, the longer-term PRAGUE-17 data are helpful in demonstrating that rates of SSE remain similar in the LAAC and NOAC groups over time, without any obvious signal of late ischemic events in the LAAC group,” he wrote.

The editorialist also called attention to the “often overlooked” issue of aspirin adherence in long-term medical therapy. Although patients treated with LAAC typically remain on aspirin indefinitely, the percentage who discontinue long-term aspirin is not well described and is not reported in PRAGUE-17. In the AVERROES trial, comparing aspirin with apixaban in patients with atrial fibrillation, however, 20.5% of patients permanently discontinued aspirin at 2 years, compared with only 17.9% on apixaban.

“It is plausible that discontinuation of aspirin may contribute to late ischemic events in patients treated with LAAC, potentially by increasing the risk of late DRT or through other mechanisms,” Dr. Merchant wrote. “Adherence to, and the impact of, long-term antiplatelet therapy should be a focus of future LAAC studies.”

The study was funded by a research grant from the Ministry of Health, Czech Republic. Dr. Osmancik reported occasional speaking honoraria from Bayer and Abbott. Dr. Merchant disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.